Oral care compositions

ABSTRACT

An oral care composition comprising high water oral care compositions comprising an orally acceptable carrier, zinc phosphate, a first stannous ion source (i.e., stannous fluoride), and a second stannous ion source (i.e., stannous chloride). Methods and uses for this composition are also described throughout.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/708,646, filed Dec. 10, 2019, which is a continuation of U.S.application Ser. No. 16/376,185, filed Apr. 5, 2019, now U.S. Pat. No.10,524,991, issued Jan. 7, 2020, which is a continuation of U.S.application Ser. No. 15/674,719, filed Aug. 11, 2017, now U.S. Pat. No.10,285,919, issued May 14, 2019, which claims priority to U.S.Provisional Application No. 62/437,102, filed Dec. 21, 2016, thecontents of each of which are incorporated herein by reference in theirentireties.

FIELD

The present invention relates to an oral care composition for use in thetreatment or prevention of erosive tooth demineralization, gingivitis,plaque, and dental caries. This oral care composition includes an orallyacceptable carrier, zinc phosphate a first stannous ion source and asecond stannous ion source.

BACKGROUND

Dental erosion involves demineralization and damage to the toothstructure due to acid attack from nonbacterial sources. Erosion is foundinitially in the enamel and, if unchecked, may proceed to the underlyingdentin. Dental erosion may be caused or exacerbated by acidic foods anddrinks, exposure to chlorinated swimming pool water, and regurgitationof gastric acids.

Dental plaque is a sticky biofilm or mass of bacteria that is commonlyfound between the teeth, along the gum line, and below the gum linemargins. Dental plaque can give rise to dental caries and periodontalproblems such as gingivitis and periodontitis. Dental caries tooth decayor tooth demineralization caused by acid produced from the bacterialdegradation of fermentable sugar.

Oral care compositions which contain stannous ion sources exhibitexcellent clinical benefits, particularly in the reduction of gingivitisand in the treatment or prevention of erosive tooth demineralization.Stannous fluoride is well known for use in clinical dentistry with ahistory of therapeutic benefits over forty years. However, untilrecently, its popularity has been limited by its instability in aqueoussolutions. The instability of stannous fluoride in water is primarilydue to the reactivity of the stannous ion (Sn²⁺). Stannous salts readilyhydrolyse above a pH of 4, resulting in precipitation from solution,with a consequent loss of the therapeutic properties.

One way to overcome the stability problems with stannous ions is tolimit the amount of water in the composition to very low levels, or touse a dual phase system. Both of these solutions to the stannous ionproblem have drawbacks. Low water oral care compositions can bedifficult to formulate with desired rheological properties, anddual-phase compositions are considerably more expensive to manufactureand package.

Soluble zinc salts, such as zinc citrate, have been used in dentifricecompositions, but have several disadvantages. Zinc ions in solutionimpart an unpleasant, astringent mouthfeel, so formulations that provideeffective levels of zinc, and also have acceptable organolepticproperties, have been difficult to achieve. Moreover, free zinc ions mayreact with fluoride ions to produce zinc fluoride, which is insolubleand so reduces the availability of both the zinc and the fluoride.Finally, the zinc ions will react with anionic surfactants such assodium lauryl sulfate, thus interfering with foaming and cleaning.

Zinc phosphate (Zn₃(PO₄)₂) is insoluble in water, although soluble inacidic or basic solutions, e.g., solutions of mineral acids, aceticacid, ammonia, or alkali hydroxides. See, e.g., Merck Index, 13^(th) Ed.(2001) p. 1812, monograph number 10205. Partly because it is viewed inthe art as a generally inert material, zinc phosphate is commonly usedin dental cements, for example in cementation of inlays, crowns,bridges, and orthodontic appliances, which are intended to endure in themouth for many years. Zinc phosphate dental cements are generallyprepared by mixing zinc oxide and magnesium oxide powders with a liquidconsisting principally of phosphoric acid, water, and buffers, so thecement comprising zinc phosphate is formed in situ by reaction withphosphoric acid.

Thus, there is a need for providing improved stannous ion containingproducts for treating or preventing erosion of tooth enamel withantimicrobial effectiveness, reducing plaque or treating or controllinggingivitis. There is also a desire for novel anti-microbial compositionsthat are stable in water and easy to manufacture.

BRIEF SUMMARY

Disclosed herein are high water oral care compositions comprising anorally acceptable carrier, zinc phosphate, a first stannous ion source(i.e., stannous fluoride), and a second stannous ion source (i.e.,stannous chloride). Methods and uses for this composition are alsodescribed throughout. The compositions disclosed herein provide improvedprotection from demineralization and enhanced antibacterial activitycompared to the prior art. In some embodiments, the zinc phosphate isadded to the dentifrice as a preformed salt. In some embodiments, theoral care composition is a toothpaste or oral gel composition.

Further areas of applicability of the present disclosure will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating the preferred embodiment of the disclosure, are intended forpurposes of illustration only and are not intended to limit the scope ofthe disclosure.

DETAILED DESCRIPTION

The following description of the preferred embodiment(s) is merelyexemplary in nature and is in no way intended to limit the disclosure,its application, or uses.

As used throughout, ranges are used as shorthand for describing each andevery value that is within the range. Any value within the range can beselected as the terminus of the range. In addition, all references citedherein are hereby incorporated by referenced in their entireties. In theevent of a conflict in a definition in the present disclosure and thatof a cited reference, the present disclosure controls.

Unless otherwise specified, all percentages and amounts expressed hereinand elsewhere in the specification should be understood to refer topercentages by weight of the entire composition. The amounts given arebased on the active weight of the material.

It has been surprisingly found that a high water oral care compositioncomprising zinc phosphate, a first stannous ion source (i.e., stannousfluoride), and a second stannous ion source (i.e., stannous chloride),selected at certain concentrations and amounts, is unexpectedly moreefficacious in boosting the anti-erosion and anti-microbial propertiesof a stannous ions containing formulation when compared to formulationsaccording to the prior art.

As used herein, the term “high water” refers to an oral carecomposition, such as a toothpaste or oral gel, which comprises from 10%to 99% water, by weight of the composition. For example, the compositionmay comprise at least 10%, 15%, 20%, 25%, 30%, 35% or 40% water, up to amaximum of, for example, 60%, 70%, 80%, 90%, 95% or 99% water, by weightof the composition. As used herein, amounts of water refer to wateradded directly to the composition, as well as water added as part ofingredients or components which are added as aqueous solutions. In someembodiments, the composition comprises 10-60% water, or 10-50% water, or10-40% water, or 10-30% water, or 15-30% water, or 15-20% water, orabout 18% water, by weight of the composition.

As used herein, the term “preformed salt”—when used in reference to zincphosphate—means that the zinc phosphate is not formed in situ in theoral care composition, e.g., through the reaction of phosphoric acid andanother zinc salt.

In one aspect, the present disclosure therefore provides a high wateroral care composition (Composition 1) comprising an orally acceptablecarrier, zinc phosphate and a first stannous ion source (i.e., stannousfluoride), and a second stannous ion source (i.e., stannous chloride).In further embodiments of this aspect, the present disclosure provides:

-   -   1.1 Composition 1, wherein the first stannous ion source        consists of a member selected from stannous fluoride, stannous        chloride, stannous acetate, stannous tartrate and sodium        stannous citrate.    -   1.2 Composition 1 or 1.1, wherein the second stannous ion source        consists of a member selected from stannous fluoride, stannous        chloride, stannous acetate, stannous tartrate, stannous oxalate        and sodium stannous citrate.    -   1.3 Any preceding composition, wherein the first stannous ion        source is stannous fluoride.    -   1.4 Any preceding composition, wherein the second stannous ion        source is stannous chloride.    -   1.5 Any preceding composition, wherein the first stannous ion        source is stannous fluoride and the second stannous ion source        is stannous chloride.    -   1.6 Any preceding composition, wherein the zinc phosphate is a        preformed salt of zinc phosphate (e.g., zinc phosphate hydrate).    -   1.7 Composition 1 or 1.2, wherein the zinc phosphate is present        in an amount sufficient so that the stannous fluoride        dissociates to provide a therapeutically effective amount of        stannous ions in aqueous solution.    -   1.8 Any preceding composition, wherein the amount of zinc        phosphate is from 0.05 to 10% by weight, relative to the weight        of the oral care composition, for example, from 0.1 to 8% by        weight, or from 0.5 to 5% by weight, or from 0.5 to 4% by        weight, or from 1 to 4%, or from 1 to 3% by weight, or from 2 to        3% by weight, or about 1% or about 2%, or about 2.35% or about        2.5%, by weight.    -   1.9 Any preceding composition, wherein the amount of the first        stannous ion source (i.e., stannous fluoride) is from 0.01% to        5% by weight, relative to the weight of the oral care        composition, for example, from 0.05 to 4% by weight, or from        0.1% to 3% by weight, or from 0.2 to 2% by weight, or from 0.3        to 1% by weight, or from 0.4 to 0.8% by weight, or from 0.4 to        0.6% by weight, or from 0.4 to 0.5% by weight, or about 0.45% by        weight (e.g., 0.454% by weight).    -   1.10 Any preceding composition, wherein the amount of the second        stannous ion source (i.e., stannous chloride) is from 0.01% to        5% by weight, relative to the weight of the oral care        composition, e.g., from 0.05 to 4% by weight, or from 0.1% to 3%        by weight, or from 0.2 to 2% by weight, or from 0.3 to 1% by        weight, or from 0.4 to 0.8% by weight, or from 0.4 to 0.6% by        weight, or from 0.4 to 0.5% by weight, or about 0.5% by weight.    -   1.11 Any preceding composition, wherein the amount of the water        is 10% by weight or more, relative to the weight of the oral        care composition, for example, 10-90%, or 10-80%, or 10-70%, or        10-60%, or 10-50%, or 10-40%, or 10-30%, or 15-30%, or 15-20%,        or about 18%, by weight of the composition.    -   1.12 Any preceding composition, further comprising an anionic        polymer selected from the group consisting of synthetic anionic        polymeric polycarboxylates, polyacrylic acids, polyphosphonic        acids, and cross-linked carboxyvinyl copolymers.    -   1.13 Composition 1.12, wherein the anionic polymer is a        copolymer of maleic anhydride or acid with another polymerizable        ethylenically unsaturated monomer, e.g., a 1:4 to 4:1 copolymer        of maleic anhydride or acid to the unsaturated monomer.    -   1.14 Composition 1.12 or 1.13, wherein the anionic polymer is a        methyl vinyl ether/maleic anhydride or acid copolymer having an        average molecular weight (M.W.) of about 30,000 to about        1,000,000, e.g., about 300,000 to about 800,000.    -   1.15 Any preceding composition, further comprising an organic        acid buffer system, e.g., a buffer system comprising a        carboxylic acid and one or more conjugate base salts thereof,        for example, alkali metal salts thereof    -   1.16 Composition 1.15, wherein the acid is selected from citric        acid, lactic acid, malic acid, maleic acid, fumaric acid, acetic        acid, succinic acid, and tartaric acid.    -   1.17 Composition 1.15 or 1.16, wherein the one or more conjugate        base salts are independently selected from sodium and potassium        salts, or combinations thereof.    -   1.18 Composition 1.15, 1.16 or 1.17 wherein the acid is citric        acid, and the one or more conjugate base salts comprise        monosodium citrate (monobasic), disodium citrate (dibasic),        trisodium citrate (tribasic), and combinations thereof.    -   1.19 Any of compositions 1.15-1.18, wherein the composition        comprises the organic acid buffer system in an amount of 0.1 to        5.0% by weight of the composition, measured as the combined        amount of organic acid and any conjugate base salts; for        example, from 0.5 to 4.0%, or from 1.0 to 3.0%, or from 1.5 to        3.0%, or from 1.0 to 2.4%, or from 1.0% to 2.0%, by weight of        the composition.    -   1.20 Any of compositions 1.15-1.19, wherein the buffer system        comprises citric acid and a sodium citrate salt (e.g., trisodium        citrate, disodium citrate, or monosodium citrate),    -   1.21 Any preceding composition, wherein the oral care        composition further comprises an abrasive, for example, silica        abrasives, calcium abrasives, and other abrasives as disclosed        herein.    -   1.22 Any preceding composition, further comprising one or more        humectants, as described herein, e.g., selected from sorbitol,        glycerol, xylitol and propylene glycol, or combinations thereof.    -   1.23 Any preceding composition, further comprising one or more        surfactants, as described herein, e.g., sodium lauryl sulfate,        sodium laureth sulfate, or cocamidopropyl betaine, or        combinations thereof    -   1.24 Any preceding composition, further comprising an effective        amount of one or more alkali phosphate salts for example        orthophosphates, pyrophosphates, tripolyphosphates,        tetraphosphates or higher polyphosphates.    -   1.25 Composition 1.24, wherein the alkali phosphate salts        comprise tetrasodium pyrophosphate or tetrapotassium        pyrophosphate, for example, in an amount of 0.5 to 5% by weight        of the composition, e.g., 1-3%, or 1-2% or about 2% by weight.    -   1.26 Composition 1.24 or 1.25, wherein the alkali phosphate        salts comprise sodium tripolyphosphate or potassium        tripolyphosphate, for example, in an amount of 0.5 to 6% by        weight of the composition, e.g., 1-4%, or 2-3% or about 3% by        weight.    -   1.27 Any preceding composition, further comprising a whitening        agent.    -   1.28 Any preceding composition, further comprising one or more        sources of zinc ions in addition to the zinc phosphate, for        example a zinc salt selected from zinc citrate, zinc oxide, zinc        lactate, zinc pyrophosphate, zinc sulfate, or zinc chloride.    -   1.29 Any preceding composition, further comprising one or more        fluoride ion sources in addition to the stannous fluoride, for        example, a fluoride ion source selected from sodium fluoride,        potassium fluoride, sodium monofluorophosphate, sodium        fluorosilicate, ammonium fluorosilicate, amine fluoride,        ammonium fluoride, and combinations thereof    -   1.30 Any preceding composition, wherein the oral care        composition is a dentifrice, e.g., a toothpaste or oral gel.    -   1.31 Any preceding composition, wherein the pH of the        composition is from 6 to 9, such as from 6.5 to 8, or from 6.5        to 7.5, or about 7.5.    -   1.32 Any preceding composition, wherein the composition is a        single-phase composition (e.g., not a dual-phase composition).    -   1.33 Any preceding composition, wherein the composition does not        comprise one or more of zinc oxide, zinc citrate, or zinc        lactate.    -   1.34 Any preceding composition, wherein the zinc phosphate is        the only zinc ion source.    -   1.35 Any preceding composition, wherein the composition is        essentially free of phosphates of more than four phosphate        groups.    -   1.36 Any preceding composition, wherein the composition is        essentially free of phosphates of more than three phosphate        groups.    -   1.37 Any preceding composition, wherein the composition is        essentially free of hexametaphosphate salts (e.g., sodium        hexametaphosphate).    -   1.38 Any preceding composition, wherein the composition is free        of citric acid and alkali metal citrate salts.    -   1.39 Any preceding composition, wherein the composition is free        of any organic acid buffer systems.    -   1.40 Any of the preceding compositions, wherein the composition        is effective upon application to the oral cavity, e.g., by        rinsing, optionally in conjunction with brushing, to (i) reduce        or inhibit formation of dental caries, (ii) reduce, repair or        inhibit pre-carious lesions of the enamel, e.g., as detected by        quantitative light-induced fluorescence (QLF) or electrical        caries measurement (ECM), (iii) reduce or inhibit        demineralization and promote remineralization of the teeth, (iv)        reduce hypersensitivity of the teeth, (v) reduce or inhibit        gingivitis, (vi) promote healing of sores or cuts in the        mouth, (vii) reduce levels of acid producing bacteria, (viii) to        increase relative levels of arginolytic bacteria, (ix) inhibit        microbial biofilm formation in the oral cavity, (x) raise and/or        maintain plaque pH at levels of at least pH 5.5 following sugar        challenge, (xi) reduce plaque accumulation, (xii) treat, relieve        or reduce dry mouth, (xiii) clean the teeth and oral        cavity (xiv) reduce erosion, (xv) prevents stains and/or whiten        teeth, (xvi) immunize the teeth against cariogenic bacteria;        and/or (xvii) promote systemic health, including cardiovascular        health, e.g., by reducing potential for systemic infection via        the oral tissues.

Any amount of zinc phosphate that is effective for protecting againstenamel erosion and/or providing any of the other benefits describedherein can be employed. Examples of suitable amounts of zinc phosphatecan range from 0.05 to 5% by weight, such as from 0.1 to 4% by weight,or from 0.5 to 3% by weight, or from 0.5 to 2% by weight, or from 0.8 to1.5% by weight, or from 0.9 to 1.1% by weight, or about 1% by weight,relative to the weight of the oral care composition.

While zinc phosphate is considered insoluble (e.g., poorly soluble), inwater, when placed in formulation, e.g., at acidic or basic pH, zincphosphate can dissolve sufficiently upon use to provide an effectiveconcentration of zinc ions to the enamel, thereby protecting againsterosion, reducing bacterial colonization and biofilm development, andproviding enhanced shine to the teeth. It has also been discovered thatzinc phosphate in a formulation with a second phosphate source enhancesphosphate deposition. As explained in WO2014/088573, the disclosure ofwhich is hereby incorporated by reference in its entirety, this is allunexpected, in view of the poor solubility of zinc phosphate, and theart-recognized view that it is substantially inert in conditions in theoral cavity, as evidenced by its widespread use in dental cement. At thesame time, the formulations containing zinc phosphate do not exhibit thepoor taste and mouthfeel, poor fluoride delivery, and poor foaming andcleaning associated with conventional zinc-based oral care products,which use more soluble zinc salts.

An amount of stannous salts, preferably stannous fluoride and/orstannous chloride in an effective amount, is employed in combinationwith the zinc phosphate in the compositions of the present disclosure.For example, the stannous fluoride and/or stannous chloride can beemployed in an amount that is effective for providing anti-microbialbenefits, such as anti-caries protection and/or anti-gingivitisprotection, and/or anti-erosion benefits for protection of tooth enamel.Examples of suitable amounts of stannous fluoride range from 0.01% to 5%by weight, relative to the weight of the oral care composition, forexample, from 0.05 to 4% by weight, or from 0.1% to 3% by weight, orfrom 0.2 to 2% by weight, or from 0.3 to 1% by weight, or from 0.4 to0.8% by weight, or from 0.4 to 0.6% by weight, or from 0.4 to 0.5% byweight, or about 0.45% by weight (e.g., 0.454%), relative to the totalweight of the dentifrice composition. Examples of suitable amounts ofstannous chloride range from 0.01% to 5% by weight, relative to theweight of the oral care composition, for example, from 0.05 to 4% byweight, or from 0.1% to 3% by weight, or from 0.2 to 2% by weight, orfrom 0.3 to 1% by weight, or from 0.4 to 0.8% by weight, or from 0.4 to0.6% by weight, or from 0.4 to 0.5% by weight, or about 0.5% by weight,relative to the total weight of the dentifrice composition. Formulationscan include stannous levels, provided by stannous fluoride, ranging forexample, from 1,000 ppm to 30,000 ppm, or from 3,000 ppm to 15,000 ppm(mass fraction) stannous ions in the total composition. In embodiments,the soluble stannous content can range from 0.1 wt % to 1.0 wt %, ormore, such as from 0.4 wt % to 0.7 wt %, based on the total weight ofthe composition.

The combination of zinc and stannous ions provides one or more of thefollowing benefits: improved antimicrobial benefits compared to the zincions alone; improved control of plaque and/or gingivitis; improvedprotection against the erosion of tooth enamel.

In compositions comprising significant amounts of water, the zincphosphate acts as a stabilizing agent for the stannous salts (i.e.,stannous fluoride and/or stannous chloride), so that the stannous saltsremain in solution in the water. As discussed above, stannous salts suchas stannous fluoride and stannous chloride are generally consideredunstable in water due to the hydrolytic and oxidative loss of stannousions at typical pH ranges employed in oral care compositions.Consequently, stannous salts are typically employed in compositionscontaining no water or low water, or with a chelating agent. Tediousprocedures are employed in order to provide stable solutions in whichthe tendency of the stannous ion to be oxidized or hydrolyzed isinhibited. Applicants have surprisingly found that zinc phosphate andstannous salts can be combined together in a single phase formulationand stabilized by the presence of an appropriate organic acid buffersystem.

The compositions may optionally comprise additional ingredients suitablefor use in oral care compositions. Examples of such ingredients includeactive agents, such as a fluoride source and/or a phosphate source inaddition to zinc phosphate. The compositions may be formulated in asuitable dentifrice base, e.g., comprising abrasives, e.g., silicaabrasives, surfactants, foaming agents, vitamins, polymers, enzymes,humectants, thickeners, additional antimicrobial agents, preservatives,flavorings, colorings, and/or combinations thereof. Examples of suitabledentifrice bases are known in the art. Alternatively, the compositionsmay be formulated as a gel (e.g., for use in a tray), chewing gum,lozenge or mint. Examples of suitable additional ingredients that can beemployed in the compositions of the present disclosure are discussed inmore detail below.

Anionic Polymer: The compositions of the disclosure may include ananionic polymer, for example, in an amount of from 1 to 20%, e.g., from5 to 20%, or from 8 to 15%, or from 10 to 14%, or from 11 to 13%, orabout 12%. Examples of such suitable anionic polymers are disclosed inU.S. Pat. Nos. 5,188,821 and 5,192,531, both of which are incorporatedherein by reference in their entirety. Suitable anionic polymers includesynthetic anionic polymeric polycarboxylates, polyacrylic acids andpolyacrylates, polyphosphonic acids, and cross-linked carboxyvinylcopolymers. Examples of synthetic anionic polymeric polycarboxylatesinclude 1:4 to 4:1 copolymers of maleic anhydride or acid with anotherpolymerizable ethylenically unsaturated monomer, preferably methyl vinylether/maleic anhydride or acid having a molecular weight (M.W.) of from30,000 to 1,000,000, such as from 300,000 to 800,000. These copolymersare available for example as Gantrez, e.g., AN 139 (M.W. 500,000), AN119 (M.W. 250,000) and preferably S-97 Pharmaceutical Grade (M.W.700,000) available from ISP Technologies, Inc., Bound Brook, N.J. 08805.Other suitable polymers include those such as the 1:1 copolymers ofmaleic anhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrollidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.Suitable generally, are polymerized olefinically or ethylenicallyunsaturated carboxylic acids containing an activated carbon-to-carbonolefinic double bond and at least one carboxyl group, that is, an acidcontaining an olefinic double bond which readily functions inpolymerization because of its presence in the monomer molecule either inthe alpha-beta position with respect to a carboxyl group or as part of aterminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrylacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomers copolymerizable with such carboxylic monomers includevinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymerscontain sufficient carboxylic salt groups for water-solubility. Afurther class of polymeric agents includes a composition containinghomopolymers of substituted acrylamides and/or homopolymers ofunsaturated sulfonic acids and salts thereof, in particular wherepolymers are based on unsaturated sulfonic acids selected fromacrylamidoalykane sulfonic acids such as 2-acrylamide 2 methylpropanesulfonic acid having a molecular weight of from 1,000 to 2,000,000.Another useful class of polymeric agents includes polyamino acidscontaining proportions of anionic surface-active amino acids such asaspartic acid, glutamic acid and phosphoserine, e.g. as disclosed inU.S. Pat. No. 4,866,161, issued to Sikes et al., which is alsoincorporated herein by reference in its entirety.

Active Agents: The compositions of the disclosure may comprise variousother agents that are active to protect and enhance the strength andintegrity of the enamel and tooth structure and/or to reduce bacteriaand associated tooth decay and/or gum disease or to provide otherdesired benefits. Effective concentration of the active ingredients usedherein will depend on the particular agent and the delivery system used.The concentration will also depend on the exact salt or polymerselected. For example, where the active agent is provided in salt form,the counterion will affect the weight of the salt, so that if thecounterion is heavier, more salt by weight will be required to providethe same concentration of active ion in the final product.

Compositions of the disclosure may contain from 0.1 to 1 wt % of anantibacterial agent, such as about 0.3 wt. %. Any suitable antimicrobialactives can be employed.

Fluoride Ion Source: The oral care compositions can include one or moreadditional fluoride ion sources, e.g., soluble fluoride salts. A widevariety of fluoride ion-yielding materials can be employed as sources ofsoluble fluoride in the present compositions. Examples of suitablefluoride ion-yielding materials are found in U.S. Pat. No. 3,535,421, toBriner et al.; U.S. Pat. No. 4,885,155, to Parran, Jr. et al. and U.S.Pat. No. 3,678,154, to Widder et al, the disclosure of each of which ishereby incorporated by reference in their entirety. Representativefluoride ion sources include, but are not limited to, sodium fluoride,potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate,ammonium fluorosilicate, amine fluoride, ammonium fluoride, andcombinations thereof. In certain embodiments the fluoride ion sourceincludes sodium fluoride, sodium monofluorophosphate as well as mixturesthereof. In certain embodiments, the oral care composition of thedisclosure may contain stannous fluoride and any additional source offluoride ions or fluorine-providing agents in amounts sufficient tosupply, in total, from 25 ppm to 25,000 ppm (mass fraction) of fluorideions, generally at least 500 ppm, e.g., from 500 to 2000 ppm, e.g., from1000 to 1600 ppm, e.g., about 1450 ppm. The appropriate level offluoride will depend on the particular application. A toothpaste forgeneral consumer use would typically have from1000 to about 1500 ppm,with pediatric toothpaste having somewhat less. A dentifrice or coatingfor professional application could have as much as 5,000 or even about25,000 ppm fluoride. Additional fluoride ion sources may be added to thecompositions of the disclosure at a level of from 0.01 wt. % to 10 wt. %in one embodiment or from 0.03 wt. % to 5 wt. %, and in anotherembodiment from 0.1 wt. % to 1 wt. % by weight of the composition. Asdiscussed above, weights of fluoride salts to provide the appropriatelevel of fluoride ion will vary based on the weight of the counterion inthe salt.

Metal Ion Source: The compositions of the present disclosure comprise ametal ion source that provides stannous ions, zinc ions, or mixturesthereof. Stannous and zinc ions have been found to help in the reductionof gingivitis, plaque, sensitivity, and improved breath benefits. Themetal ion source can be a soluble or a sparingly soluble compound ofstannous or zinc with inorganic or organic counter ions. Examplesinclude the fluoride, chloride, chlorofluoride, acetate,hexafluorozirconate, sulfate, tartrate, gluconate, citrate, malate,glycinate, pyrophosphate, metaphosphate, oxalate, phosphate, carbonatesalts and oxides of stannous and zinc.

Stannous and zinc ions are derived from the metal ion source(s) found inthe dentifrice composition in an effective amount. An effective amountis defined as from at least about 1000 ppm metal ion, preferably about2,000 ppm to about 15,000 ppm. More preferably, metal ions are presentin an amount from about 3,000 ppm to about 13,000 ppm and even morepreferably from about 4,000 ppm to about 10,000 ppm. This represents thetotal amount of metal ions (stannous and zinc and mixtures thereof) thatis present in the compositions for delivery to the tooth surface.

Dentifrices containing stannous salts, particularly stannous fluorideand stannous chloride, are described in U.S. Pat. No. 5,004,597. Otherdescriptions of stannous salt dentifrices are found in U.S. Pat. No.5,578,293. The preferred stannous salts are stannous fluoride andstannous chloride dihydrate. Other suitable stannous salts includestannous acetate, stannous tartrate, stannous oxalate and sodiumstannous citrate. Examples of suitable zinc ion sources are zinc oxide,zinc sulfate, zinc chloride, zinc citrate, zinc lactate, zinc gluconate,zinc malate, zinc tartrate, zinc carbonate, zinc phosphate, and othersalts listed in U.S. Pat. No. 4,022,880.

Abrasives: The compositions of the disclosure can include abrasives.Examples of suitable abrasives include silica abrasives, such asstandard cleaning silicas, high cleaning silicas or any other suitableabrasive silicas. Additional examples of abrasives that can be used inaddition to or in place of the silica abrasives include, for example, acalcium phosphate abrasive, e.g., tricalcium phosphate (Ca₃(PO₄)₂),hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂), or dicalcium phosphate dihydrate(CaHPO₄.2H₂O, also sometimes referred to herein as DiCal) or calciumpyrophosphate; calcium carbonate abrasive; or abrasives such as sodiummetaphosphate, potassium metaphosphate, aluminum silicate, calcinedalumina, bentonite or other siliceous materials, or combinationsthereof.

Silica abrasive polishing materials useful herein, as well as the otherabrasives, generally have an average particle size ranging between 0.1and 30 microns, such as between 5 and 15 microns. The silica abrasivescan be from precipitated silica or silica gels, such as the silicaxerogels described in U.S. Pat. No. 3,538,230, to Pader et al. and U.S.Pat. No. 3,862,307, to Digiulio, the disclosures of which areincorporated herein by reference in their entireties. Particular silicaxerogels are marketed under the trade name Syloid® by the W. R. Grace &Co., Davison Chemical Division. The precipitated silica materialsinclude those marketed by the J. M. Huber Corp. under the trade nameZeodent®, including the silica carrying the designation Zeodent 105, 115and 119. These silica abrasives are described in U.S. Pat. No.4,340,583, to Wason, the disclosure of which is incorporated herein byreference in its entirety. In certain embodiments, abrasive materialsuseful in the practice of the oral care compositions in accordance withthe disclosure include silica gels and precipitated amorphous silicahaving an oil absorption value of less than 100 cc/100 g silica, such asfrom 45 cc/100 g to 70 cc/100 g silica. Oil absorption values aremeasured using the ASTA Rub-Out Method D281. In certain embodiments, thesilicas are colloidal particles having an average particle size of from3 microns to 12 microns, and from 5 to 10 microns. Examples of low oilabsorption silica abrasives useful in the practice of the disclosure aremarketed under the trade designation Sylodent XWA® by Davison ChemicalDivision of W.R. Grace & Co., Baltimore, Md. 21203. Sylodent 650 XWA®, asilica hydrogel composed of particles of colloidal silica having a watercontent of 29% by weight averaging from 7 to 10 microns in diameter, andan oil absorption of less than 70 cc/100 g of silica is an example of alow oil absorption silica abrasive useful in the practice of the presentdisclosure.

Any suitable amount of silica abrasive can be employed. Examples ofsuitable amounts include 10 wt. % or more dry weight of silicaparticles, such as from 15 wt. % to 30 wt. % or from 15 wt. % to 25 wt.%, based on the total weight of the composition.

Foaming agents: The oral care compositions of the disclosure also mayinclude an agent to increase the amount of foam that is produced whenthe oral cavity is brushed. Illustrative examples of agents thatincrease the amount of foam include, but are not limited topolyoxyethylene and certain polymers including, but not limited to,alginate polymers. The polyoxyethylene may increase the amount of foamand the thickness of the foam generated by the oral care compositions ofthe present disclosure. Polyoxyethylene is also commonly known aspolyethylene glycol (“PEG”) or polyethylene oxide. The polyoxyethylenessuitable for compositions of the present disclosure may have a molecularweight of from 200,000 to 7,000,000. In one embodiment the molecularweight may be from 600,000 to 2,000,000 and in another embodiment from800,000 to 1,000,000. Polyox® is the trade name for the high molecularweight polyoxyethylene produced by Union Carbide. The foaming agent,(e.g., polyoxyethylene) may be present in an amount of from 0.1% to 50%,in one embodiment from 0.5% to 20% and in another embodiment from 1% to10%, or from 2% to 5% by weight of the oral care compositions of thepresent disclosure.

Surfactants: The compositions useful in the compositions of the presentdisclosure may contain anionic surfactants, for example:

-   -   i. water-soluble salts of higher fatty acid monoglyceride        monosulfates, such as the sodium salt of the monosulfated        monoglyceride of hydrogenated coconut oil fatty acids such as        sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride        sulfate,    -   ii. higher alkyl sulfates, such as sodium lauryl sulfate,    -   iii. higher alkyl-ether sulfates, e.g., of formula        CH₃(CH₂)_(m)CH₂(OCH₂CH₂)_(n)OSO₃X, wherein m is 6-16, e.g., 10,        n is 1-6, e.g., 2, 3 or 4, and X is Na or K, for example sodium        laureth-2 sulfate (CH₃(CH₂)₁₀CH₂(OCH₂CH₂)₂OSO₃Na),    -   iv. higher alkyl aryl sulfonates such as sodium dodecyl benzene        sulfonate (sodium lauryl benzene sulfonate),    -   v. higher alkyl sulfoacetates, such as sodium lauryl        sulfoacetate (dodecyl sodium sulfoacetate), higher fatty acid        esters of 1,2 dihydroxy propane sulfonate, sulfocolaurate        (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl        sarcosinate.

By “higher alkyl” is meant, e.g., C₆₋₃₀ alkyl. In certain embodiments,the anionic surfactants useful herein include the water-soluble salts ofalkyl sulfates having from 10 to 18 carbon atoms in the alkyl radicaland the water-soluble salts of sulfonated monoglycerides of fatty acidshaving from 10 to 18 carbon atoms. Sodium lauryl sulfate, sodium lauroylsarcosinate and sodium coconut monoglyceride sulfonates are examples ofanionic surfactants of this type. In particular embodiments, the anionicsurfactant is selected from sodium lauryl sulfate and sodium etherlauryl sulfate. In a particular embodiment, the compositions of thedisclosure comprise sodium lauryl sulfate. The anionic surfactant may bepresent in an amount which is effective, e.g., >0.01% by weight of theformulation, but not at a concentration which would be irritating to theoral tissue, e.g., <10%, and optimal concentrations depend on theparticular formulation and the particular surfactant. In one embodiment,the anionic surfactant is present in a toothpaste at from 0.3% to 4.5%by weight, e.g., about 1.5%. The compositions of the disclosure mayoptionally contain mixtures of surfactants, e.g., comprising anionicsurfactants and other surfactants that may be anionic, cationic,zwitterionic or nonionic. Generally, suitable surfactants are thosewhich are reasonably stable throughout a wide pH range. Surfactants aredescribed more fully, for example, in U.S. Pat. No. 3,959,458, toAgricola et al.; U.S. Pat. No. 3,937,807, to Haefele; and U.S. Pat. No.4,051,234, to Gieske et al, the disclosures of which are incorporatedherein by reference in their entireties.

The surfactant or mixtures of compatible surfactants that are includedin addition to the anionic surfactants can be present in thecompositions of the present disclosure in from 0.1% to 5.0%, in anotherembodiment from 0.3% to 3.0% and in another embodiment from 0.5% to 2.0%by weight of the total composition. These ranges do not include theanionic surfactant amounts.

In some embodiments, the compositions of the present disclosure includea zwitterionic surfactant, for example a betaine surfactant, for examplecocamidopropylbetaine, e.g. in an amount of from 0.1% to 4.5% by weight,e.g. from 0.5 to 2% by weight cocamidopropylbetaine.

Tartar control agents: In various embodiments of the present disclosure,the compositions comprise an anticalculus (tartar control) agent.Suitable anticalculus agents include, without limitation, phosphates andpolyphosphates (for example pyrophosphates and tripolyphosphates),polyaminopropanesulfonic acid (AMPS), hexametaphosphate salts, zinccitrate trihydrate, polypeptides, polyolefin sulfonates, polyolefinphosphates, and diphosphonates. The compositions of the disclosure thusmay comprise phosphate salts in addition to the zinc phosphate. Inparticular embodiments, these salts are alkali phosphate salts, e.g.,salts of alkali metal hydroxides or alkaline earth hydroxides, forexample, sodium, potassium or calcium salts. “Phosphate” as used hereinencompasses orally acceptable mono- and polyphosphates, for example,P₁₋₆ phosphates, for example monomeric phosphates such as monobasic,dibasic or tribasic phosphate; and dimeric phosphates such aspyrophosphates; and multimeric phosphates, such as tripolyphosphates,tetraphosphates, hexaphosphates and hexametaphosphates (e.g., sodiumhexametaphosphate). In particular examples, the selected phosphate isselected from alkali dibasic phosphate and alkali pyrophosphate salts,e.g., selected from sodium phosphate dibasic, potassium phosphatedibasic, dicalcium phosphate dihydrate, calcium pyrophosphate,tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodiumtripolyphosphate, and mixtures of any of two or more of these. In aparticular embodiment, for example the compositions may comprisetetrasodium pyrophosphate in an amount of from 0.5 to 5% by weight,e.g., 1-3%, or 1-2% or about 2% by weight of the composition. In anotherembodiment, the compositions may comprise a mixture of tetrasodiumpyrophosphate (TSPP) and sodium tripolyphosphate (STPP), e.g., inproportions of TSPP at from 0.5 to 5 wt. %, such as from 1 to 2 wt. %,e.g., 2 wt. %, and STPP at from 0.5% to 6 wt. %, such as 1 to 4%, or 2to 3% by weight of the composition. Such phosphates are provided in anamount effective to reduce erosion of the enamel, to aid in cleaning theteeth, and/or to reduce tartar buildup on the teeth, for example in anamount of from 0.2 to 20 wt. %, e.g., from 1 to 15 wt. %, by weight ofthe composition.

Aqueous Buffer System: In some embodiments, the compositions of thedisclosure further comprise an organic acid buffer system, e.g., abuffer system comprising a carboxylic acid and one or more conjugatebase salts thereof, for example, alkali metal salts thereof. The acidmay be, for example, selected from citric acid, lactic acid, malic acid,maleic acid, fumaric acid, acetic acid, succinic acid, and tartaricacid. The one or more conjugate base salts may be independently selectedfrom sodium and potassium salts, or combinations thereof. In certainembodiments, the organic acid is citric acid, and the one or moreconjugate base salts comprise monosodium citrate (monobasic), disodiumcitrate (dibasic), trisodium citrate (tribasic), and combinationsthereof. The composition may comprise the organic acid buffer system inany effective amount, for example, in an amount of 0.1 to 5.0% by weightof the composition, measured as the combined amount of organic acid andany conjugate base salts. For example, the composition may comprise theorganic acid buffer system in an amount of from 0.5 to 4.0%, or from 1.0to 3.0%, or from 1.5 to 3.0%, or from 1.0 to 2.4%, or from 1.0% to 2.0%,by weight of the composition. In some embodiments, the ratio of acid toconjugate base may be, for example, from 1:1 to 1:10, e.g., from 1:2 to1:8, or from 1:3 to 1:6, or from 1:4 to 1:6, or from 1:5 to 1:6, orabout 1:5, by weight of the components. In other embodiments, the ratioof acid to conjugate base may be reversed, e.g., from 1:1 to 10:1, e.g.,from 2:1 to 8:1, or from 6:1 to 3:1, or from 4:1 to 6:1 or about 5:1, byweight of the components. In particular embodiments, the buffer systemcomprises citric acid and a sodium citrate salt (e.g., trisodiumcitrate, disodium citrate, or monosodium citrate), in a ratio of from1:3 to 1:6, or 1:4 to 1:6, or 1:5, by weight.

Flavoring Agents: The oral care compositions of the disclosure may alsoinclude a flavoring agent. Flavoring agents which are used in thepractice of the present disclosure include, but are not limited to,essential oils as well as various flavoring aldehydes, esters, alcohols,and similar materials. Examples of the essential oils include oils ofspearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus,marjoram, cinnamon, lemon, lime, grapefruit, and orange. Also useful aresuch chemicals as menthol, carvone, and anethole. Certain embodimentsemploy the oils of peppermint and spearmint. The flavoring agent may beincorporated in the oral composition at a concentration of from 0.1 to5% by weight e.g., from 0.5 to 1.5% by weight.

Other Polymers: The oral care compositions of the disclosure may alsoinclude additional polymers to adjust the viscosity of the formulationor enhance the solubility of other ingredients. Such additional polymersinclude polyethylene glycols, polysaccharides (e.g., cellulosederivatives, for example carboxymethyl cellulose, hydroxymethylcellulose, ethyl cellylose, microcrystalline cellulose or polysaccharidegums, for example xanthan gum, guar gum or carrageenan gum). Acidicpolymers, for example polyacrylate gels, may be provided in the form oftheir free acids or partially or fully neutralized water soluble alkalimetal (e.g., potassium and sodium) or ammonium salts. In one embodiment,the oral care composition may contain PVP. PVP generally refers to apolymer containing vinylpyrrolidone (also referred to asN-vinylpyrrolidone, N-vinyl-2-pyrrolidione and N-vinyl-2-pyrrolidinone)as a monomeric unit. The monomeric unit consists of a polar imide group,four non-polar methylene groups and a non-polar methane group.

In some embodiments, the compositions of the disclosure comprise one ormore polyethylene glycols, for example, polyethylene glycols in amolecular weight range from 200 to 800. For example, the compositionsmay comprise one or more of polyethylene glycol 200, polyethylene glycol300, polyethylene glycol 400, polyethylene glycol, 600 or polyethyleneglycol 800.

Silica thickeners, which form polymeric structures or gels in aqueousmedia, may be present. Note that these silica thickeners are physicallyand functionally distinct from the particulate silica abrasives alsopresent in the compositions, as the silica thickeners are very finelydivided and provide little or no abrasive action. Other thickeningagents are carboxyvinyl polymers, carrageenan, hydroxyethyl celluloseand water soluble salts of cellulose ethers such as sodium carboxymethylcellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gumssuch as karaya, gum arabic, and gum tragacanth can also be incorporated.Colloidal magnesium aluminum silicate can also be used as component ofthe thickening composition to further improve the composition's texture.In certain embodiments, thickening agents in an amount of from 0.5% to5.0% by weight of the total composition are used.

Humectants: Within certain embodiments of the oral compositions, it isalso desirable to incorporate a humectant to prevent the compositionfrom hardening upon exposure to air. Certain humectants can also impartdesirable sweetness or flavor to dentifrice compositions. Suitablehumectants include edible polyhydric alcohols such as glycerin,sorbitol, xylitol, propylene glycol as well as other polyols andmixtures of these humectants. In one embodiment of the disclosure, theprincipal humectant is one of glycerin, sorbitol or a combinationthereof. The humectant may be present at levels of greater than 15 wt.%, such as from 15 wt. % to 55 wt. %, or from 20 wt. % to 50 wt. %, orfrom 20 wt. % to 40 wt. %, or about 20% or about 30% or about 40%, basedon the total weight of the composition.

Other optional ingredients: In addition to the above-describedcomponents, the embodiments of this disclosure can contain a variety ofoptional oral care ingredients some of which are described below.Optional ingredients include, for example, but are not limited to,adhesives, sudsing agents, flavoring agents, sweetening agents such assodium saccharin, additional antiplaque agents, abrasives, aestheticssuch as TiO₂ coated mica or other coloring agents, such as dyes and/orpigments.

In some embodiments, the compositions of the present disclosure can haveany pH suitable for in a product for use in oral care. Examples ofsuitable pH ranges are from 6 to 9, such as from 6.5 to 8, or 6.5 to7.5, or about 7.0.

In some embodiments, the oral care compositions of the presentdisclosure are either essentially free of, free of, or do not includeany sodium hexametaphosphate. In some embodiments, the oral carecompositions of the present disclosure are either essentially free of,free of, or do not include any halogenated diphenyl ethers (e.g.,triclosan).

By “essentially free” is meant that the compositions have no more than0.01% by weight of these compounds.

In some embodiments, the compositions of the present disclosure areeither essentially free of, free of or do not include any complexingagents for increasing solubility of zinc phosphate and/or formaintaining the stannous fluoride in solution. Examples of knowncomplexing agents that can be excluded from the compositions of thepresent disclosure include the chelating agents taught in U.S. PatentApplication No. 2007/0025928, the disclosure of which is herebyincorporated by reference in its entirety. Such chelating agents includemineral surface-active agents, including mineral surface-active agentsthat are polymeric and/or polyelectrolytes and that are selected fromphosphorylated polymers, wherein if the phosphorylated polymer is apolyphosphate, the polyphosphate has average chain length of 3.5 ormore, such as 4 or more; polyphosphonates; copolymers of phosphate- orphosphonate-containing monomers or polymers with ethylenicallyunsaturated monomers, amino acids, proteins, polypeptides,polysaccharides, poly(acrylate), poly(acrylamide), poly(methacrylate),poly(ethacrylate), poly(hydroxyalkylmethacrylate), poly(vinyl alcohol),poly(maleic anhydride), poly(maleate) poly(amide), poly(ethylene amine),poly(ethylene glycol), poly(propylene glycol), poly(vinyl acetate) andpoly(vinyl benzyl chloride); and mixtures thereof. Other knowncomplexing agents that can be excluded from the compositions of thepresent disclosure include those taught in CA 2634758, the disclosure ofwhich is incorporated here by reference in its entirety. Examplesinclude polyphosphorylated inositol compounds such as phytic acid,myo-inositol pentakis(dihydrogen phosphate); myo-inositoltetrakis(dihydrogen phosphate), myo-inositol trikis(dihydrogenphosphate), and alkali metal, alkaline earth metal or ammonium salts ofany of the above inositol compounds. Phytic acid is also known asmyo-inositol 1,2,3,4,5,6-hexakis (dihydrogen phosphate) or inositolhexaphosphoric acid.

In another aspect, the present disclosure provides a method of treatmentor prevention of erosive tooth demineralization, gingivitis, plaque,and/or dental caries, the method comprising the application to the oralcavity of a person in need thereof a composition according to theinvention (e.g., Composition 1.0 et seq), e.g., by brushing, forexample, one or more times per day.

In another aspect, the present disclosure provides a method of using thecompositions described herein (e.g., any of Compositions 1.0 et seq) toincrease zinc levels in the enamel and to treat, reduce or control theincidence of enamel erosion. The methods comprise applying any of thecompositions as described herein to the teeth, e.g., by brushing, orotherwise administering the compositions to the oral cavity of a subjectin need thereof. The compositions can be administered regularly, suchas, for example, one or more times per day. In various embodiments,administering the compositions of the present disclosure to a patientcan provide one or more of the following benefits: (i) reducehypersensitivity of the teeth, (ii) reduce plaque accumulation, (iii)reduce or inhibit demineralization and promote remineralization of theteeth, (iv) inhibit microbial biofilm formation in the oral cavity, (v)reduce or inhibit gingivitis, (vi) promote healing of sores or cuts inthe mouth, (vii) reduce levels of acid producing bacteria, (viii)increase relative levels of non-cariogenic and/or non-plaque formingbacteria, (ix) reduce or inhibit formation of dental caries, (x) reduce,repair or inhibit pre-carious lesions of the enamel, e.g., as detectedby quantitative light-induced fluorescence (QLF) or electrical cariesmeasurement (ECM), (xi) treat, relieve or reduce dry mouth, (xii) cleanthe teeth and oral cavity, (xiii) reduce erosion, (xiv) whiten teeth;(xv) reduce tartar build-up, and/or (xvi) promote systemic health,including cardiovascular health, e.g., by reducing potential forsystemic infection via the oral tissues. The disclosure further providescompositions for use in any of the above methods. Further embodimentsprovide methods wherein at least one tooth is remineralized afteradministration of a composition as described herein.

The present application further discloses a method of making any of thecompositions of the present disclosure. The method comprises combiningzinc phosphate and stannous fluoride in water to form an aqueous zincphosphate mixture. In some embodiments, the zinc phosphate is added tothe dentifrice composition as a preformed salt and remains essentiallyinsoluble in the aqueous mixture. The amount of water employed in themixture can be any of the amounts recited herein for the compositions ofthe present disclosure. Any standard mixing techniques can be employedto combine the ingredients and form a stable composition without theneed for additional complexing agents to solubilize the stannous ionsources, such as any of the above disclosed complexing or chelatingagents, or the use of anhydrous mixing techniques such as dissolvingstannous salts in an anhydrous material such as glycerin.

EXAMPLES Example 1—Dentifrice Formulation

Representative Dentifrice Formulations according to the presentdisclosure are prepared according to Table 1 below:

TABLE 1 Ingredient Weight % Water  15-20 Humectants  15-55 Abrasives 10-30 Thickeners 0.5-5 Polymers 0.5-5 Zinc Phosphate 0.05-5  Flavor,Sweetener, Colors 0.5-5 Alkali Phosphate Salts 0.5-5 Anionic Surfactant0.01-10 Zwitterionic Surfactant  0.1-4.5 Organic Acid Buffer Acid (e.g.Citric Acid)  0.0-3.0 Stannous Fluoride 0.01-2  Stannous Chloride0.01-2 

An experimental formulation (Formulation 1) according to the presentdisclosure is shown in Table 2. A comparative composition (ComparativeExample), which contains only a single source of stannous (i.e.,stannous fluoride), is also shown in Table 2. Ingredients in Table 2 arelisted by weight percent of the composition. A commercial zinclactate/stannous fluoride toothpaste composition (CommercialFormulation) was also used for comparison. The formulation of this isshown in Table 3.

TABLE 2 Comparative Formulation 1 Example Ingredient (wt. %) (wt. %)Water 18.3 18.3 Humectants (Sorbitol, Glycerin, 47.8 48.5 PolyethyleneGlycol) Thickeners 1.5 1.5 Sodium Carboxymethyl Cellulose 0.8 0.8Xanthan Gum 0.3 0.3 Microcrystalline Cellulose 1.0 1.0 Abrasives 21.5 20Zinc Phosphate, hydrate 1.0 1.0 Flavor, Sweetener, Color 2.4 2.3Tetrasodium Pyrophosphate 2.0 2.0 Anionic Surfactant 1.5 1.5Zwitterionic Surfactant 1.25 1.25 Trisodium Citrate, Dihydrate 1.0 1.0Citric Acid- Anhydrous 0.2 0.2 Stannous Fluoride 0.454 0.454 StannousChloride 0.5 —

TABLE 3 Ingredient % w/w Comm. Ex. Water and minors (color, flavor) 9.50Stannous fluoride  0.454 Stannous chloride — Zinc lactate 2.50 Zincphosphate — Thickeners 3.15 Glycerin 34.65  Abrasive silica 20.00 Sodium Hexametaphosphate 13.00  Propylene Glycol 7.00 Trisodium CitrateDihydrate — Polyethylene Glycol 600 7.00 Tetrasodium Pyrophosphate —Anionic Surfactant 1.00 Trisodium Phosphate 1.10 Zwitterionic Surfactant— Sodium Gluconate 0.65 Sodium Carboxymethyl Cellulose — Xanthan GumMicrocrystalline Cellulose Citric Acid —

Example 2—Stannous and Zinc Uptake

The two dentifrice compositions shown above were compared in a stannousand zinc ion uptake experiments using Vitro-Skin, a substrate thatmimics the surface properties of human skin.

Metal ion uptake is measured using the Vitro-Skin soft tissue protocol.Vitro-Skin (IMS Inc., Portland, Me.) is cut into uniform circles of20-21 mm diameter, and the circles are rinsed in bulk with hexane andair dried to remove the silicone coating. After soaking the circles insterilized, clear human saliva for three hours, the saliva is removedand the Vitro-Skin circles are added to a fresh slurry of the testcomposition in water (1 mL of slurry formed from 2.0 g composition plus4 mL water). After incubating for 10 minutes at 37° C., the slurry isremoved and the Vitro-skin circles are rinsed three times with distilledwater. The circles are then soaked overnight in 1 mL of concentratednitric acid. After dilution to a volume of 10 mL with distilled water,the resulting mixture is analyzed for stannous and zinc concentration byatomic absorption spectroscopy. Uptake is measured in units of microgramper square centimeter based on both sides of the Vitro-Skin circletested.

The results indicated that the combination of zinc phosphate, stannousfluoride and stannous chloride in Formulation 1 resulted insubstantially increased uptake of both stannous and zinc ions comparedto the Commercial Formulation, which lacked stannous chloride andcontained zinc lactate instead of zinc phosphate. Specifically, Formula1 surprisingly showed about a 50% improvement in stannous uptake, andabout a 500% increase in zinc uptake. With regard to the ComparativeExample, which included only one stannous source, showed a modestincrease in stannous uptake and over a 1000% increase in zinc uptake.These results heavily implicate that a combination of zinc phosphate,stannous fluoride and stannous chloride results in highly superioractive ion availability and uptake in situ.

Example 3—Active Ion Availability and Stability Test

Formulations containing zinc phosphate, stannous fluoride and stannouschloride were tested for stability and availability of active metal andflouride ions over a 13-week period of time. Initial measurements ofavailable amounts of stannous, zinc, and fluoride ions were taken atroom temperature. Samples were broken up into two groups: one that wastested at room temperature conditions, and another that was tested underaccelerated aging conditions at 40° C. Measurements were taken at 4weeks, 8 weeks and 13 weeks to test for concentration of availablestannous, zinc and fluoride. Results are shown below.

Formulation 1 as defined above in Table 2 was tested for stability data.The results are shown in Table 4.

TABLE 4 Available Available Available Stannous Zinc fluoride AgingDuration (wt. %) (wt. %) (ppm) Initial (25° C.) 0.49 0.28 1114 4 weeks(25° C./40° C.) 0.52/0.48 0.29/0.31  1058/1001 8 weeks (25° C./40° C.)0.48/0.43 0.28/0.27 1054/967 13 weeks (25° C./40° C.) 0.41/0.370.28/0.25 1031/858

An additional formulation similar to Formulation 1 was tested forstability data, which is summarized below in Table 5. This additionalformulation contained similar components as in Formulation 1, but didnot contain any trisodium citrate/citric acid buffer.

TABLE 5 Available Available Available Stannous Zinc fluoride AgingDuration (wt. %) (wt. %) (ppm) Initial (25° C.) 0.53 0.13 1065 4 weeks(25° C./40° C.) 0.35/0.27 0.13/0.13 997/958 8 weeks (25° C./40° C.)0.40/0.33 0.12/0.12 784/857 13 weeks (25° C./40° C.) 0.35/0.17 0.13/0.13983/893

As illustrated above, the composition of Formulation 1 exhibitedexceptional stability for each of the tested active ions. Formulation 1showed almost no loss of available zinc over the entire testing period,even under accelerated aging conditions. Formulation 1 also proved to besurprisingly stable with respect to stannous and fluoride, losing onlyabout 24% and 23% of available stannous and fluoride, respectively, overthe entire testing period under accelerated aging conditions.Formulation 1 showed much higher overall stability when compared to theformulation having no trisodium citrate/citric acid buffer. Inparticular, Formulation 1 showed far superior stability of availablestannous over the testing period, with the formulation having notrisodium citrate/citric acid buffer showing a 68% loss of availablestannous after 13 weeks at accelerated aging conditions.

While the present invention has been described with reference toembodiments, it will be understood by those skilled in the art thatvarious modifications and variations may be made therein withoutdeparting from the scope of the present invention as defined by theappended claims.

The invention claimed is:
 1. A high water oral care compositioncomprising: an orally acceptable carrier; zinc phosphate, wherein theamount of zinc phosphate is present in an amount of from 0.05 to 10% byweight, relative to the weight of the oral care composition; a firststannous ion source, from 0.01% to 5% by weight, wherein the firststannous ion source is stannous fluoride; a second stannous ion source,from 0.01% to 5% by weight, wherein the second stannous ion source isstannous chloride; wherein the amount of the water is 10%-90% by weightor more, relative to the weight of the oral care composition; and one ormore humectants selected from sorbitol, glycerol, xylitol, propyleneglycol, and combinations thereof.
 2. A composition according to claim 1,wherein the zinc phosphate is a preformed salt of zinc phosphate.
 3. Acomposition according to claim 1, wherein the amount of the water is10%-30% by weight, relative to the weight of the oral care composition.4. A composition according to claim 1, further comprising one or moresurfactants selected from sodium lauryl sulfate, sodium laureth sulfate,or cocamidopropyl betaine, or combinations thereof.
 5. A compositionaccording to claim 1, further comprising an effective amount of one ormore alkali phosphate salts.
 6. A composition according to claim 5,wherein the alkali phosphate salts comprise tetrasodium pyrophosphate ortetrapotassium pyrophosphate.
 7. A composition according to claim 1,further comprising one or more sources of zinc ions in addition to thezinc phosphate.
 8. A composition according to claim 1, furthercomprising an organic acid buffer system comprising a carboxylic acidand one or more conjugate base salts thereof.
 9. A composition accordingto claim 1, wherein the oral care composition is a dentifrice.
 10. Amethod of treatment or prevention of erosive tooth demineralization,gingivitis, plaque, and/or dental caries, the method comprising theapplication to the oral cavity of a person in need thereof a compositionaccording to claim
 1. 11. A method to to (i) reduce or inhibit formationof dental caries, (ii) reduce, repair or inhibit pre-carious lesions ofthe enamel, (iii) reduce or inhibit demineralization and promoteremineralization of the teeth, (iv) reduce hypersensitivity of theteeth, (v) reduce or inhibit gingivitis, (vi) promote healing of soresor cuts in the mouth, (vii) reduce levels of acid producing bacteria,(viii) to increase relative levels of arginolytic bacteria, (ix) inhibitmicrobial biofilm formation in the oral cavity, (x) raise and/ormaintain plaque pH at levels of at least pH 5.5 following sugarchallenge, (xi) reduce plaque accumulation, (xii) treat, relieve orreduce dry mouth, (xiii) clean the teeth and oral cavity (xiv) reduceerosion, (xv) prevents stains and/or whiten teeth, (xvi) immunize theteeth against cariogenic bacteria; and/or (xvii) promote systemichealth, including cardiovascular health.